The FGF/FGFR signalling mediated anti-cancer drug resistance and therapeutic intervention

Mahapatra, Subhasmita; Jonniya, Nisha Amarnath; Koirala, Suman; Ursal, Kapil Dattatray; Kar, Parimal

doi:10.1080/07391102.2023.2191721

Cited by 10 publications

(9 citation statements)

References 215 publications

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“… 26 In mammals, there are 22 members of the FGFs family, which can be classified into endocrine, paracrine, typical autocrine, and intracellular FGFs. 27 Canonical FGFs include paracrine and autocrine subfamilies, which can bind and trigger the activation of fibroblast growth factor receptors (FGFRs). FGF/FGFR signaling network influences oncogenesis through a variety of mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor 11 (FGF11) Promotes Progression and Cisplatin Resistance Through the HIF-1α/FGF11 Signaling Axis in Ovarian Clear Cell Carcinoma

Yin¹,

Lu²,

Zhou³

et al. 2023

CMAR

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Background A poor prognosis is often associated with ovarian clear cell carcinoma (OCCC) due to its relative resistance to platinum-based chemotherapy. Although several studies have been launched to explore the pathogenesis of OCCC, the mechanism of chemoresistance has yet to be uncovered. Methods Nanostring nCounter PanCancer Pathways Panel was performed to explore the expression profiles of OCCC tissues from patients showing different platinum sensitivity. Bioinformatic analysis was performed to select genes associated with chemoresistance and cell function assays, including colony formation, wound healing, transwell and flow cytometric analysis, were used to explore the role of the target gene in the progression of OCCC and resistance to cisplatin (DDP). Results Gene expression profiles and bioinformatic analysis verified that the expression of fibroblast growth factor 11 (FGF11) was significantly increased in platinum-resistant OCCC tissues and increased FGF11 expression was related to poorer survival. Downregulation of FGF11 inhibited the proliferation, migration, and invasion, reversing the DDP resistance of OCCC cells. Mechanically, FGF11 was regulated by hypoxia-inducible factor-1α (HIF-1α) to modulate the DDP sensitivity. Conclusion FGF11 was highly expressed in platinum-resistant OCCC tissues, promoting progression and resistance to DDP through the HIF-1α/FGF11 signaling axis.

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Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor 11 (FGF11) Promotes Progression and Cisplatin Resistance Through the HIF-1α/FGF11 Signaling Axis in Ovarian Clear Cell Carcinoma

Yin¹,

Lu²,

Zhou³

et al. 2023

CMAR

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“…FGFs, especially FGF-1, also have a wound healing-promoting effect in cases of wound healing disorders. FGFR signaling can also lead to the activation of various downstream effectors, such as cell, survival, migration, and differentiation [8,25,51]. These functions are essential for normal development and tissue homeostasis.…”

Section: Chemical Structures Of Fgfsmentioning

confidence: 99%

The Role of Fibroblast Growth Factor-Receptor Pathway Aberrations in Pediatric Diseases

Bittmann,

Luchter,

Moschüring-Alieva

2024

AJPR

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The fibroblast growth factor receptors play a crucial role in binding to fibroblast growth factor and are involved in various pathological conditions. These receptors consist of an extracellular ligand domain, a transmembrane helix domain, and an intracellular domain with tyrosine kinase activity. There are over 48 different isoforms of FGFR. Each FGF receptor in ligand-binding properties and kinase domains. The FGF/FGFR signaling pathway is implicated in various pediatric cancers and therefore are both non-selective and selective FGFR inhibitors available. Additionally, there are five distinct membrane FGF receptors dentified in vertebrates. All belonging to the tyrosine kinase superfamily. In this manuscript, the focus is based on an analysis of the role of FGF receptor signaling pathways and aberrations especially in pediatric diseases. Erk 1 and Erk 2 seem to have an important role as a mediator of FGF signaling in different biological and developmental processes. FGF signaling plays an important role in conserved developmental functions in skeletal growth, palate closure, ear development, cranial suture ossification and neuronal development in the child. Aberrant FGF signaling causes different congenital disorders and different forms of cancer in childhood. Modulating FGF signaling is of great importance for the treatment of rare diseases in childhood.

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“…Second generation FGFR inhibitors are more selective including FGFR 1-3 inhibitors (pemigatinib, infigratinib, AZD4547, Debio1347), FGFR 1-4 inhibitors (erdafitinib, rogaratinib) and selective FGFR 4 inhibitor (fisogatinib) [7]. Despite their potential anti-tumor activity, they are ineffective at overcoming commonly acquired FGFR gatekeeper mutations (FGFR1 V561M, FGFR2 V564F, FGFR3 V555M, FGFR4 V550M/L) and other mutations including FGFR1 N546K mutation and FGFR2 N550H mutations [71][72][73]. Third generation FGFR inhibitors such as futibatinib (TAS-120) can covalently bind to a highly conserved cysteine residue (Cys488 in FGFR1c) in FGFR kinase, and cannot be readily replaced by ATP, thus prolonging the duration of activity, and overcoming secondary FGFR2 resistance mutations in patients with infigratinib or Debio1347 resistance [7].…”

Section: Generations Of Fgfr Inhibitorsmentioning

confidence: 99%

“…Given that a single agent FGFR inhibition treatment could cause intrinsic and acquired resistance, the combination of FGFR inhibitors with chemotherapy, immunotherapy and targeted therapy combination could be considered for both synergistic effect and reduction of drug resistance development [73]. FGFR inhibitors can enhance tumor sensitivity to chemotherapy drugs including irinotecan, paclitaxel, 5-fluorouracil, and etoposide in human oncogenic cells with aberrant FGFR activation in vitro studies [134].…”

Section: Future Therapeutic Combinations With Fgf/fgfr Inhibitorsmentioning

confidence: 99%

Molecular Targeting of the Fibroblast Growth Factor Receptor (FGFR) Pathway Across Various Cancers

Shan,

Dalal,

Thaw Dar

et al. 2023

Preprint

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Fibroblast growth factor receptors (FGFRs) are a family of receptor tyrosine kinases that involve in regulation of cell proliferation, survival, and development. FGFR alterations including amplifications, fusions, rearrangements, and mutations can result downstream activation of tyrosine kinases leading to tumor development. Targeting those FGFR alterations has shown to be effective in cholangiocarcinoma, urothelial carcinoma, and myeloid/lymphoid neoplasms and there are currently four FGFR inhibitors approved by the Food and Drug Administration (FDA). There have been developments of multiple agents targeting FGFR pathway including selective FGFR inhibitors, ligand traps, monoclonal antibodies, and antibody drug conjugates. However, most of these agents have variable and low responses with some intolerable toxicities and acquired resistances. This review will summarize previous clinical experiences and current developments of agents targeting FGFR pathway and discuss future directions of FGFR targeting agents.

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The FGF/FGFR signalling mediated anti-cancer drug resistance and therapeutic intervention

Cited by 10 publications

References 215 publications

Fibroblast Growth Factor 11 (FGF11) Promotes Progression and Cisplatin Resistance Through the HIF-1α/FGF11 Signaling Axis in Ovarian Clear Cell Carcinoma

Fibroblast Growth Factor 11 (FGF11) Promotes Progression and Cisplatin Resistance Through the HIF-1α/FGF11 Signaling Axis in Ovarian Clear Cell Carcinoma

The Role of Fibroblast Growth Factor-Receptor Pathway Aberrations in Pediatric Diseases

Molecular Targeting of the Fibroblast Growth Factor Receptor (FGFR) Pathway Across Various Cancers

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